Local anesthetic formulation, which is one type of transdermal absorption formulation, has been widely used for the purpose of relieving pain generated during a medical treatment such as intravenous indwelling needle puncture or skin minor surgery. In Japan, as such a local anesthetic formulation, a tape agent of lidocaine (Penles (registered trademark)) has been commercially available. This tape agent is a formulation prepared by allowing an acrylic pressure-sensitive adhesive to comprise lidocaine crystals (concentration: 60%), and according to the Package insert of this tape agent, it is described that when the agent is used for pain relief during intravenous indwelling needle puncture, it is attached to the puncture target site for approximately 30 minutes. However, it has also been reported that, in order to obtain sufficient effects of pain relieving, it is necessary to attach the agent for 100 minutes on average (Non Patent Literature 1). Hence, from the viewpoint of medication management or a problem regarding an increase in burden on patients, it has been desired to reduce the time, at which anesthetic effects are expressed, in actual medical sites.
On the other hand, as transdermal absorption preparations for local anesthesia, combination drugs each comprising two types of local anesthetics, such as a mixture of lidocaine and prilocaine or a mixture of lidocaine and tetracaine, have been proposed. It has been known that such a combination drug exhibits an excellent local anesthetic action, when compared with administration of a single local anesthetic agent. In fact, a cream formulation (Emla Cream), oil in water emulsion of a mixture of lidocaine and prilocaine, has been commercially available, and this cream formulation has been confirmed to have a higher anesthetic action than a cream formulation comprising lidocaine alone and prilocaine alone (Patent Literature 1). However, in order to achieve sufficient pain relieving effects from this cream agent, it has been necessary to spread the present cream agent to the skin such that the cream is thickly heaped up thereon, and further, to apply an occlusive dressing technique (ODT) using a film or the like. Thus, this cream agent has been problematic in terms of complicated procedures.
In view of the foregoing, a simple tape agent comprising a mixture of lidocaine and prilocaine as a drug has also been proposed (Patent Literature 2). Patent Literature 2 discloses a prescription of using a crosslinked acrylic pressure-sensitive adhesive, and when compared with the previous lidocaine tape agent (Penles (registered trademark)), this formulation has been confirmed to have the fast-acting property of anesthesia. Nevertheless, as a result of the studies conducted by the present inventors, it has been revealed that the skin permeability of the drug (in vitro test) used as an indicator of the expression of medicinal effects is inferior to the previous cream agent, and that the skin permeability is approximately 2 times higher than that of Penles (registered trademark).
Moreover, as a local anesthetic, a water-soluble patch comprising a mixture of lidocaine and prilocaine or a mixture of lidocaine and tetracaine has also been proposed (Patent Literature 3). But in general, such a water-soluble patch has been problematic in that its adhesiveness is lower than that of a water-insoluble tape agent, and thus, it is easily dropped out from the skin.
Shingles is a disease, which is caused by infection with varicella or shingles virus, and skin rash is generated along the dermatome of an area supplied by a nerve, and pain also appears due to such skin rash. In a majority of shingles patients, such pain disappears with the recovery of skin rash. In some patients, however, shingles is shifted to postherpetic neuralgia, in which pain remains even after the recovery of skin rash. Postherpetic neuralgia is caused by the damage or degeneration of the peripheral nervous fibers of a patient infected with varicella or shingles virus, and this disease is classified into neuropathic pain. Since intolerable pain symptoms such as shooting pain or allodynia, which are hardly experienced in daily life, continuously occur, the QOL of patients with postherpetic neuralgia is significantly reduced. With regard to the aforementioned water-soluble patch, Lidoderm (a 5% lidocaine poultice preparation, Endo Pharmaceuticals Inc.) has been placed on the market as a therapeutic agent for postherpetic neuralgia in the United States of America, and according to the guidelines of International Association for the Study of Pain, Lidoderm is determined to be a first-line drug for superficially localized neuropathic pain. However, taking into consideration its long application time such as attachment for 12 hours, this patch agent always has the risk of being dropped out from the skin because of its weak adhesive force, and thus, it is highly likely that the original therapeutic effects cannot be obtained due to such dropping out. In addition, since the therapeutic effects of Lidoderm are not necessarily high (Non Patent Literature 2), it has been desired to develop a patch having higher therapeutic effects for postherpetic neuralgia.